Share This

Scientists have shown that a brand new type of cancer pill that exploits the emerging field of epigenetics is safe for human use, according to a Phase I trial reported May 1 in Clinical Cancer Research.

Related Articles

Instead of targeting faults in the DNA code, the drug -- discovered in a collaboration between The Institute of Cancer Research (ICR) and Chroma Therapeutics -- targets cancer-causing errors in the way the body reads the DNA code.

This second and equally important set of instructions takes the form of a series of chemical switches that determine whether genes are turned on or off, and ultimately what the cell will look like and how it will function.

Epigenetics influence nature in many ways including the ability of a caterpillar to morph into a butterfly, even though its DNA does not change. Alterations in epigenetic control can also lead to cancer.

Lead author Dr Udai Banerji from the ICR and The Royal Marsden says: "This is a new angle of attack against cancer. Scientists are already working hard to design drugs that target many cancer genes, but there is also huge potential in targeting these epigenetic changes. Although epigenetics is a normal part of biology, faults in epigenetic switches can cause cancer by switching on oncogenes or switching off tumour suppressing genes."

The new drug acts on an enzyme called histone deacetylase (HDAC), which normally regulates gene expression -- by switching genes on and off -- via modification of the proteins that package and order DNA, called histones.

Of all known epigenetic targets, scientists have made the most progress in developing inhibitors for HDAC, with two HDAC inhibiting drugs already licensed to treat a type of lymphoma. However, these existing drugs have limitations, including significant side-effects and for one of them the need for injections.

The next-generation HDAC drug, CHR-3996, has been designed so it selectively inhibits one type of HDAC enzyme (class one), which the collaborative team hopes will reduce side-effects associated with existing treatments while retaining its anti-cancer properties. It killed a range of different cancer cell types in laboratory testing.

In a Phase I study carried out in the Drug Development Unit of the ICR and The Royal Marsden, and the Erasmus University Medical Center in Rotterdam, CHR-3996 was tested in 39 patients with a range of advanced cancers.

"First-generation HDAC inhibitors have already demonstrated that this class of drugs can be effective for some cancer patients. The objective here was to develop a more specific drug that would be better tolerated, and could be formulated so it can be administered as tablets rather than an injection to maximize patient comfort and safety," Dr Banerji says. "We found that CHR-3996 was active when taken in pill form, and the side-effects were favourable."

The trial was primarily designed to assess safety, but one patient's pancreatic tumours shrunk, and nine other patients were shown to have stable disease for at least two months. Blood tests revealed that the drug was reaching its target, and was present in a concentration that was sufficient to cause tumours to shrink in pre-clinical models.

CHR-3996 is one of 16 innovative drug candidates discovered over the past five years in the ICR's Cancer Research UK Cancer Therapeutics Unit, and one of six taken into Phase I clinical trials at the ICR and The Royal Marsden's Drug Development Unit.

Professor Paul Workman, Director of the Cancer Research UK Cancer Therapeutics Unit at the ICR, says: "It very gratifying to see promising results from the first stage of clinical evaluation for this epigenetic drug, which was discovered through a collaboration between Chroma Therapeutics and The Institute of Cancer Research. We are looking forward to seeing the results of larger-scale patient trials."

The study was sponsored by Chroma Therapeutics while the Drug Development Unit receives infrastructural funding from Cancer Research UK, ECMC and the NIHR.

Dr Joanna Reynolds, Cancer Research UK's director of centres, said: "This 'epigenetic' approach to therapy -- which targets chemical switches rather than DNA -- is an exciting new avenue for drug discovery and it's great to see rapid progress being made in this field. We look forward to seeing the results of further trials, which will aim to discover whether this pill can help improve cancer survival in patients with advanced disease."

The Institute of Cancer Research. "Next-generation 'epigenetic' cancer pill shown to be safe in phase I trial." ScienceDaily. ScienceDaily, 1 May 2012. <www.sciencedaily.com/releases/2012/05/120501085508.htm>.

The Institute of Cancer Research. (2012, May 1). Next-generation 'epigenetic' cancer pill shown to be safe in phase I trial. ScienceDaily. Retrieved March 3, 2015 from www.sciencedaily.com/releases/2012/05/120501085508.htm

The Institute of Cancer Research. "Next-generation 'epigenetic' cancer pill shown to be safe in phase I trial." ScienceDaily. www.sciencedaily.com/releases/2012/05/120501085508.htm (accessed March 3, 2015).

More From ScienceDaily

More Health & Medicine News

Featured Research

Mar. 3, 2015 — Children of recently separated or divorced families are likelier to drink sugar-sweetened beverages than children in families where the parents are married, putting them at higher risk for obesity ... full story

Mar. 3, 2015 — Gastric bypass and similar stomach-shrinking surgeries are a popular option for obese patients looking to lose weight or treat type 2 diabetes. While the surgeries have been linked to a decreased ... full story

Mar. 3, 2015 — Most people consume more salt than they need and therefore have a higher risk of heart disease and stroke, which are the two leading causes of death worldwide. But a new study reveals that dietary ... full story

Mar. 3, 2015 — Twice as many children born to mothers who took antibiotics during pregnancy were diagnosed with asthma by age 3 than children born to mothers who didn’t take prenatal antibiotics, a new study has ... full story

Mar. 3, 2015 — Pediatric otolaryngologists and surgeons are concerned with parents getting the wrong message regarding the safety/desirability of letting babies and young children eat peanuts to prevent them from ... full story

Mar. 3, 2015 — Why do people shake hands? A new study suggests one of the reasons for this ancient custom may be to check out each other's odors. Even if we are not consciously aware of this, handshaking may ... full story

Mar. 3, 2015 — It appears that stress markers in unemployed people can be found, independent of smoking, alcohol consumption and overweight/obesity. Results from a study suggest that long-term unemployment may be ... full story

Mar. 3, 2015 — Doctors write millions of prescriptions a year for drugs to calm the behavior of people with Alzheimer’s disease and other types of dementia. But non-drug approaches actually work better, and carry ... full story

Featured Videos

Mom Triumphs Over Tragedy, Helps Other Families

AP (Mar. 3, 2015) — After her son, Dax, died from a rare form of leukemia, Julie Locke decided to give back to the doctors at St. Jude Children&apos;s Research Hospital who tried to save his life. She raised $1.6M to help other patients and their families. (March 3)
Video provided by AP

Woman Convicted of Poisoning Son

AP (Mar. 3, 2015) — A woman who blogged for years about her son&apos;s constant health woes was convicted Monday of poisoning him to death by force-feeding heavy concentrations of sodium through his stomach tube. (March 3)
Video provided by AP

Related Stories

Sep. 8, 2014 — A new drug targeting mitochondrial function in human cancer cells was safe and showed some efficacy in a Phase I clinical trial. These data suggest that agents targeting mitochondrial metabolism can ... full story

Sep. 19, 2011 — Scientists have pioneered a new combination treatment for prostate cancer. The treatment, which has been successful in phase one of trials, will now be tested for efficacy in a second ... full story

Apr. 21, 2011 — The SWOG trial S0421 closed early based on interim finding that atrasentan added to docetaxel and prednisone did not confer additional survival benefit to patients with advanced hormone-refractory ... full story

ScienceDaily features breaking news and videos about the latest discoveries in health, technology, the environment, and more -- from major news services and leading universities, scientific journals, and research organizations.